Investigations of the pathways and controls of epidermal protein synthesis in mammalian tissue will be extended during the next grant period. Epidermal ribonuclease will be characterized and inhibitors of its action will be developed for use in the in vitro protein synthesizing which are central to our efforts. Initially from animal model systems and subsequently from normal and pathologic human epidermis, the nascent epidermal proteins will be identified and they will be related to two known structural components of epidermis, keratin and keratohyalin. The nascent precursors of keratin and keratohyalin will then be isolated and characterized by biochemical,biophysical and immunologic techniques. The site of synthesis of the precursors and the mechanism by which their synthesis is controlled will be studied. Topical therapy of hyperplastic epidermal disease in man will be the ultimate aim of studies of the effects of inhibitors of epidermal protein synthesis at transcriptional and translational levels.